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Biomedical subjects

B K Nelson

Publications and source records attributed to B K Nelson.

At least 55 records · Page 3Linked to original sources
PubMed1981

Ethoxyethanol behavioral teratology in rats.

2-ethoxyethanol, a solvent developed for nitrocellulose and also used in lacquers, dyes, varnish removers, and in numerous industrial processes, was evaluated for possible functional effects in offspring of rats exposed during gestation. A dose finding study revealed that no offspring survived inhalation exposure (7 hours/day) from gestation days 7-13 or 14-20 at 900 ppm, and there were approximately 34 percent neonatal deaths even after prenatal exposure to 200 ppm-the current Federal occupational standard. Consequently, pregnant Sprague-Dawley rats were exposed to 100 ppm ethoxyethanol for 7 hours/day on gestation days 7-13 or 14-20. The only effect observed in the mothers was slightly prolonged gestation in he mothers exposed on days 14-20 of gestation (p less than .001). Behavioral testing of offspring from dams exposed to ethoxyethanol on gestation days 7-13 revealed: (a) impaired performance on a rotorod test of neuromuscular ability (p = .002); (b) prolonged latency of leaving the start area of an open field (p = .009); and (c) marginal superiority in avoidance conditioning begun on day 34 of age (p = 061). Offspring from dams exposed to ethoxyethanol on gestation days 14-20: (a) were less active than controls in a running wheel (p = 0.32), and (b) received an increased number and duration of shocks in avoidance conditioning begun on day 60 of age (p = .004). Neurochemical evaluation of whole-brain samples from newborn pups revealed significantly decreased levels of norepinephrine in offspring from both exposure periods (p less than .01). In regional analyses of brains from 21-day-old offspring of dams exposed to 100 ppm ethoxyethanol on gestation days 7-13, the cerebrum had significant elevations in acetylcholine (p less than .01), norepinephrine ( p less than .01), and dopamine (p less than .05), the cerebellum had nearly a 3-fold increase in acetylcholine (p less than .01); the brainstem had an increase in norepinephrine (p less than 0.01); and the midbrain had excesses of acetylcholine (p less than .01), norepinephrine (p less than .05) and protein (p less than .05). In brains from 21-day-old offspring of dams exposed to ethoxyethanol on gestation days 14-20, the cerebrum had significant elevations in acetylcholine, dopamine, and 5-hydroxytryptamine (p less than .05). Overall, the results indicate that there are behavioral and neurochemical alterations in offspring of rats following prenatal exposure to 100 ppm ethoxyethanol.

Animals↗
PubMed1980

Locoweed embryotoxicity in rats.

In an effort to develop a laboratory animal assay for locoweed (Astragalus lentiginosus and Astragalus wootoni) teratogenicity, different amounts of the plant were administered either in feed pellets or by gavage to rats. In preliminary experiments with A. lentiginosus in feed pellets, we found dose-dependent effects on the number of pups born alive and on birth weight of pups. In the primary experiment, 1 gm of A. lentiginosus or A. wootoni administered by gavage on Days 7 through 17 of gestation produced similar results. A. lentiginosus reduced pup birth weights by 13% less than that of controls; this weight differential persisted for at least 4 weeks. A. lentiginosus also reduced the number of offspring born alive (34.9% fewer than those of controls) and the number of survivors to weaning (86.4% fewer than that of controls). No gross malformations were observed. Behavioral tests, however, showed that activity patterns of 30-day-old offspring of dams fed locoweed differed from those of pups of control dams. A test of learning indicated no differences. At 80 days of age, offspring of treated dams showed no significant differences from those of control dams. The same behavioral tests also showed no differences among the dams at the time of testing. Microscopic examination of tissues from pups whose mothers had been given locoweed revealed lesions only in the newborn pups. Neural lesions were not observed even in the newborn pups. Dose-dependent and species-dependent embryotoxic effects of locoweed were observed in rats.

Animals↗
PubMedDate not supplied

Interactions of radiofrequency radiation on 2-methoxyethanol teratogenicity in rats.

Concurrent exposures to chemical and physical agents occur in the workplace; exposed workers include those involved with microelectronics industry, plastic sealers and electrosurgical units. Previous animal research indicates that hyperthermia induced by an elevation in ambient temperature can potentiate the toxicity and teratogenicity of some chemical agents. We previously demonstrated that combined exposure to radiofrequency (r.f.; 10 MHz) radiation, which also induces hyperthermia and is teratogenic to exposed animals, and the industrial solvent 2-methoxyethanol (2ME) produces enhanced teratogenicity in rats. A subsequent study replicated and extended that research by investigating the interactive dose-related teratogenicity of r.f. radiation (sham exposure or maintaining colonic temperatures at 42.0 degrees C for 0, 10, 20 or 30 min by r.f. radiation absorption) and 2ME (0, 75, 100, 125 or 150 mg/kg) on gestation days 9 or 13 of rats. The purpose of the present research is to determine the effects of r.f. radiation (sufficient to maintain colonic temperatures at 42.0 degrees C for 10 min) on a range of doses of 2ME (0, 20, 40, 60, 80, 100, 120 and 140 mg kg-1) administered on gestation day 13 of rats. Focusing on characterizing the dose-response pattern of interactions, this research seeks to determine the lowest interactive effect level. Day 20 fetuses were examined for external and skeletal malformations. The results are consistent with previous observations. Dose-related developmental toxicity was observed for 2ME both in the presence and absence of r.f. radiation. However, concurrent RF radiation exposure changed the shape of the dose-effect curve of 2ME. These data indicate that combined exposure effects should be considered when developing exposure guidelines and intervention strategies.

Abnormalities, Drug-Induced↗
PubMedDate not supplied

Snake envenomation. Incidence, clinical presentation and management.

Snake envenomation is a major cause of death and disability in the developing countries, particularly India and Southeast Asia. Species variation in venom components, yield, and lethality leads to quite different clinical presentations and mortality. Venomous snakes are divided into 5 families. Bites of the Viperidae, Crotalidae and Colubridae usually cause primarily local effects and bleeding; the Elapidae most commonly cause neurological symptoms, particularly paralysis; while the Hydrophidae cause paralysis and myolysis. Venoms are complex mixtures of enzymes, peptides and metalloproteins. 26 enzymes have been identified, and 10 of those are found in most venoms. Components have been identified that act as procoagulants, anticoagulants, hyaluronidases, RNases, DNases, postsynaptic toxins and presynaptic toxins. Other peptides induce capillary leak syndrome, haemolysis and shock. The clinical results of envenomation vary widely, and there may be no envenomation with a bite. Syndromes reported include oedema, haemolysis, shock, bleeding, pituitary failure, renal failure, myonecrosis, and combinations of the above. First aid measures that have been proposed include tourniquets, constricting bands, tight crepe bandages, incision and suction, cryotherapy, and high voltage electric shock. None of these has been shown to be effective except usage of a crepe bandage for Australian elapid bite. Tourniquets or cryotherapy, if used for extended periods may lead to gangrene. The most important first aid measure is rapid transport to comprehensive medical care. There is some controversy about medical treatment in the United States, but less in other countries. Supportive measures routinely required include intravenous fluids, tetanus prophylaxis and antibiotics. Anticholinergics may be useful in elapid bite. Intubation and ventilation may be necessary. Unproven surgical approaches include excision of envenomated tissues and fasciotomy. The former is disfiguring, the latter should be reserved for those patients with demonstrated increased intracompartmental pressure. More than 100 antivenins are produced by about 36 laboratories worldwide. The products are effective, but carry a high risk of serum sickness and a lesser risk of anaphylaxis. A more effective and less reactive product is under development.

Africa↗
PubMedDate not supplied

Neurochemical, but not behavioral, deviations in the offspring of rats following prenatal or paternal inhalation exposure to ethanol.

In addition to its widespread social use, ethanol is used extensively as an industrial solvent. Inhalation exposures to ethanol which produce narcosis in maternal rats are not teratogenic. The present study sought to extend the previous research by including offspring from paternal exposures, and testing for behavioral disorders in the offspring following maternal or paternal exposures. Groups of 18 male (approximately 450 g) and 15 female (200-300 g) Sprague-Dawley rats were exposed 7 hours/day for six weeks or throughout gestation to 16000, 10000, or 0 ppm ethanol by inhalation and then mated with untreated rats. Litters were culled to 4 males and 4 females, and were fostered within 16 hours after birth to untreated dams which had delivered their litters within 48 hours previously. Offspring from paternally or maternally exposed animals performed as well as controls on days 10-90 in tests of neuromotor coordination (ascent on a wire mesh screen, rotorod), activity levels (open field, modified-automated open field, and running wheel), and learning ability (avoidance conditioning and operant conditioning). In addition, brains of 10 21-day-old pups were analyzed for neurochemical differences from controls in concentrations of protein and the neurotransmitters acetylcholine, dopamine, norepinephrine, 5-hydroxytryptamine, substance P, Met-enkephalin, and beta-endorphin. Levels of acetylcholine, dopamine, substance P, and beta-endorphin were essentially unchanged in the offspring of rats exposed to ethanol. Complex, but significant changes in levels of norepinephrine occurred only in paternally exposed offspring. 5-Hydroxytryptamine levels were reduced in the cerebrum, and Met-enkephalin levels were increased in all brain regions of offspring from both maternally and paternally exposed rats.

Administration, Inhalation↗
PubMedDate not supplied

Behavioral teratology investigation of 1-propanol administered by inhalation to rats.

Due to their structural similarity to ethanol, a human teratogen, and their widespread use in industry, a series of industrial alcohols are being investigated for developmental toxicity. This paper presents the results of exposures to 7000 ppm 1-propanol, which is minimally toxic to maternal animals and produces a low incidence of teratogenicity, and to 3500 ppm 1-propanol, which is not toxic to maternal rats and produces no teratogenicity. Propanol vapors or filtered air was administered for 7 hr/day to 15 pregnant Sprague-Dawley rats throughout gestation or to 18 male rats daily for 6 weeks. Tests of offspring were: a) ascent on a wire mesh screen b) rotorod, c) open field and optically monitored activity, d) running wheel, e) avoidance conditioning, and f) progressive fixed ratio schedule of reinforcement. Brains from 10 rats per group were dissected into cerebrum, cerebellum, brainstem, and midbrain, and were assayed for protein, acetylcholine, dopamine, norepinephrine, serotonin, beta-endorphin, Met-enkephalin, and substance P. Overall, the results indicate that exposure to high concentrations of 1-propanol can affect fertility in exposed males (only 2 of 17 produced litters), but there were no consistent effects seen in the behavioral or neurochemical tests measured. This lack of effects is surprising based on predictions from the structural similarity of 1-propanol to ethanol, and on long-standing observations that toxicity (to adult animals) increases with carbon chain length among the aliphatic alcohols.

1-Propanol↗
PubMedDate not supplied

Effects of 2-methoxyethanol on fetal development, postnatal behavior, and embryonic intracellular pH of rats.

The industrial solvent 2-methoxyethanol (2ME) is a reproductive and developmental toxicant when administered by inhalation, gavage, and IP injection. The present research established that this solvent can produce teratogenicity in rats when administered in liquid diet. Groups of 10 Sprague-Dawley rats were given various percentages of 2ME in liquid diet on gestation days 7-18. Day 20 fetuses were examined for visceral or skeletal malformations. Concentrations above 0.025% 2ME (approximately 73 mg/kg/day) produced total embryo-mortality. Cardiovascular malformations were produced at lower levels. The teratogenic no-effect level was 0.006% 2ME (16 mg/kg). In a second experiment, groups of 12 Sprague-Dawley rats were given 0, 0.006 and 0.012% of 2ME as above. Litters were culled to 8 pups, and tested for auditory and tactile startle and conditioned lick suppression, and for performance in figure-8 activity and the Cincinnati water maze on postnatal days 48-65. The high dose of 2ME produced approximately 50% mortality in the offspring and increased the number of errors in the Cincinnati maze. No other behavioral effects were observed at either dose. An interaction study was conducted to determine if simultaneous exposure to 2ME and ethanol would reduce the teratogenicity of 2ME, but no reduction was observed. The hypothesis that 2ME acts by altering embryonic intracellular pH was tested by injecting 0.33 ml/kg of 2ME into rats on gestation day 13, and determining embryonic intracellular pH at 2, 4, 8, and 24 hours thereafter. There was an increase in pH at 4 hours, but not at later time points. Another group of rats was given 2ME along with amiloride, which blocks the sodium/hydrogen antiporter. The combined 2ME-amiloride exposure produced an incidence of cardiovascular malformations in fetuses twice that of 2ME alone. These studies confirmed the structural teratogenicity of 2ME even when given in liquid diet, as it was given for the first time in the present study. At nonteratogenic doses, developmental toxicity (e.g., postnatal deaths) persisted, but only limited evidence of behavioral teratogenicity was observed. The pH data are consistent with the concept that 2ME may alter embryonic intracellular pH at critical stages of organogenesis.

Abnormalities, Drug-Induced↗
PubMedDate not supplied

Behavioral teratology investigation of 1-butanol in rats.

Two concentrations of 1-butanol (3000 and 6000 ppm) were administered by inhalation to separate groups of 15 pregnant Sprague-Dawley rats for 7 hr per day throughout gestation; 18 male rats were similarly exposed for 7 hr per day for 6 weeks, and mated to unexposed females. Litters were culled to 4 female and 4 male pups and fostered to untreated controls. From days 10-90, offspring were tested as follows: a) ascent on a wire mesh screen, b) rotorod, c) open field and photoelectrically-monitored activity, d) running wheel, e) avoidance conditioning, and f) operant conditioning. Additionally, brains from 10 offspring at 21 days of age were dissected into cerebrum, cerebellum, brainstem, and midbrain. Each sample was assayed for protein and the neurotransmitters acetylcholine, dopamine, norepinephrine, serotonin, met-enkephalin, beta-endorphin, and substance P. Overall, there were few behavioral or neurochemical alterations detected in the offspring following maternal or paternal exposure to either 3000 or 6000 ppm 1-butanol. This scarcity of effects is important to risk assessment extrapolations drawn from ethanol. Based on the structural similarity of 1-butanol to ethanol and long-standing observations that toxicity to adult animals generally increases with chain length among the alcohols, significant behavioral and neurochemical deviations were predicted. The scarcity of effects from butanol needs to be accounted for in hypotheses relating toxicity to alcohol chain length and in risk assessment extrapolations from findings with ethanol.

Animals↗
PubMedDate not supplied

Origins of behavioral teratology and distinctions between research on pharmaceutical agents and environmental/industrial chemicals.

Most behavioral teratology studies have focused on pharmaceutical agents. Investigations of developmental toxicity are lacking for the majority of the nearly 100,000 industrial chemicals currently in use. Only some three dozen chemicals have been examined for behavioral/neurochemical deviations in offspring following maternal exposures. Examination of industrial agents for developmental toxicity, therefore, remains a major public health need. Most developmental research addresses the effects of pharmaceutical agents, but these studies frequently do not address environmental/industrial concerns due to fundamental differences in experimental methodology. The route, duration, and timing of exposure, usefulness of fostering of offspring, and potential concomitant exposure of both parents are all variables which should be treated differently in research on industrial chemicals as opposed to pharmaceutical agents. After briefly tracking the history of behavioral teratology, the present paper discusses differences in application of behavioral teratological principles to industrial versus pharmaceutical agents, and points to the largely untested number of industrial chemicals needing investigation.

Abnormalities, Drug-Induced↗
PubMedDate not supplied

Selecting exposure parameters in developmental neurotoxicity assessments.

Numerous factors must be considered in selecting exposure parameters for developmental neurotoxicity investigations. Whether employing a single dose during pregnancy, or continuous exposure from prepregnancy through early postnatal developmental periods, the following primary factors should be addressed: 1) Purpose of the study; 2) pharmacokinetics/pharmacodynamics; 3) biotransformation; 4) genotypic variables; 5) limiting factors, including the availability of test compounds for evaluation; and, 6) several general, miscellaneous factors. Whether a single, large dose of an exogenous agent is more toxic to the developing nervous system than a series of smaller doses depends upon the interaction of the physicochemical, pharmacokinetic, and pharmacodynamic properties of the agent with the genotypic features of the test organism.

Aging↗